Degenerative Eye Disease

Glaucoma is a progressive optic neuropathy characterised by the neurodegeneration of the retinal ganglion cells (RGCs) resulting in irreversible visual impairment and eventual blindness if untreated. In glaucoma, damage and degeneration of RGCs and their axons result in characteristic changes in the appearance of the optic nerve head and patterns of visual field loss. Glaucoma is the leading cause of irreversible blindness worldwide and is estimated to affect over 60 million people globally; a number which is predicted to 118.8 million by 2040.  Primary open angle glaucoma (POAG) is the commonest subtype of glaucoma and pseudo-exfoliation glaucoma (PXFG) is the most prevalent type of secondary open angle glaucoma. The pathogenesis of POAG is multifactorial and complex but currently lowering intra-ocular pressure (IOP) medically or surgically is the only modifiable risk factor. Our research is multidisciplinary and is centred on two main themes:

1. Molecular therapies for ocular disease targeting the underlying genetics and molecular disturbances resulting in ocular pathology. We have established an ex vivo anterior segment perfusion model to study glaucoma, develop new therapies and evaluate drug delivery. We have several RNA and molecular therapies in pre-clinical evaluation for glaucoma. This includes a novel bispecific antibody developed within Ulster University to target neuro-inflammation in glaucoma. These therapeutic approaches may also be relevant to other common eye diseases including age-related macular degeneration and diabetic retinopathy.

2. Personalised or stratified medicine for eye disease. Using genetic information to determine disease risk, disease stratification and to predict treatment response/pharmacogenetics. We have an active multicentre study investigating the genetic basis of steroid glaucoma and improve the clinical surveillance and treatment of patients. With collaborators in Liverpool and Lancaster we are developing AI tools to better detect glaucoma in the developing world and UK/Ireland.

The Genomic Medicine Research Group at Ulster focus on identifying the mutations which cause ocular surface disorders and in doing so they facilitate improved diagnosis and treatment in the ageing or diseased eye. This work has resulted in discovery of a number of highly disruptive mutations and subsequently development of preclinical models allowing assessment of gene therapy in a mutation or allele specific approach, paving the way for cutting edge therapeutics to be applied to the eye. The ultimate goal is to move forward how eye diseases are treated in the clinical setting with the ability to quickly detect the disease causing mutation, screen all family members, predict who will develop the disease and in a preventative measure treat prior to any damage to the delicate ocular surface occurs, thus retaining sight.

The group have focused on siRNA silencing of the mutant allele and are also developing some novel knock out replacement strategies. It is anticipated that a patient could be given eye drop formulations containing a very precise siRNA designed specifically for the mutation they carry and when applied to the front of the eye this siRNA will enter the cells and act almost like an eraser deleting all the mistaken, mutation encoded messengers which cause the disease symptoms to appear. This approach brings together stratified medicine and personalised treatment in what is now termed Precision Medicine.